Famciclovir (famciclovir)

Famciclovir is metabolized mainly in the liver to the active drug penciclovir. In patients with well-compensated chronic liver disease such as chronic hepatitis, chronic alcohol abuse, or primary biliary cirrhosis, bioavailability of penciclovir was not affected. Therefore, modification of famciclovir dosage is not necessary in patients with well-compensated liver disease. The manufacturer does not make specific recommendations for patients with uncompensated hepatic impairment, since the pharmacokinetics of famciclovir has not been evaluated in these patients.

Famciclovir is eliminated mainly by the kidneys via tubular secretion and glomerular filtration. In patients with moderately or severely impaired renal function, the frequency of administration of famciclovir should be decreased in response to the degree of impairment as indicated by creatinine clearance.

Because penciclovir (the active metabolite) is readily removed from plasma during hemodialysis, famciclovir should be administered after each hemodialysis session when the drug is used for the treatment of herpes zoster, treatment of recurrent mucocutaneous HSV infections in HIV-infected patients, or suppression of recurrent genital herpes. Famciclovir is administered once as a single dose after a hemodialysis session when the drug is used for the treatment of recurrent genital herpes or treatment of recurrent herpes labialis. The manufacturer recommends that a famciclovir dose (250 mg for patients with herpes zoster, 250 mg for HIV-infected patients with recurrent mucosal or cutaneous HSV infection, or 125 mg for patients receiving the drug for suppression of recurrent genital herpes) be administered following each hemodialysis session. The manufacturer recommends that a famciclovir dose (250 mg for patients with recurrent genital herpes, 250 mg for patients with recurrent herpes labialis) be administered once as a single dose after a hemodialysis session.

Famciclovir is administered orally without regard to meals. Food does not affect the systemic bioavailability or elimination of famciclovir.

Famciclovir not metabolized by CYP isoenzymes.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Famciclo; Val; Acyclovir/Varicella; Zoster Live Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Acyclovir, famciclovir, and valacyclovir inhibit varicella zoster virus activity and may prevent the body from developing an immune response to the live vaccine.

CLINICAL EFFECTS: Administration of antiviral agents active against varicella zoster virus may decrease the efficacy of live, attenuated varicella or zoster vaccines.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: CDC immunization guidelines recommend acyclovir, famciclovir or valacyclovir discontinuation at least 24 hours prior to administration of varicella or zoster vaccines, if possible. Delay use or resumption of antiviral therapy for 14 days after vaccination.(1)

DISCUSSION: Acyclovir, famciclovir, valacyclovir inhibit varicella zoster virus activity and may prevent the body from developing an immune response to the live vaccine, decreasing the efficacy of efficacy of live, attenuated varicella or zoster vaccines.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Selected Antivirals/Talimogene Laherparepvec

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Talimogene laherparepvec is a live, attenuated herpes simplex virus (HSV-1) which has been modified to express human GM-CSF.(1)

CLINICAL EFFECTS: Administration of antiviral agents with activity against HSV-1 may interfere with the effectiveness of talimogene laherparepvec.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concomitant use when possible. Talimogene laherparepvec is a live, attenuated herpes simplex virus (HSV-1) which is injected into cancerous lesions where it replicates and produces GM-CSF, leading to lysis of tumors. It is sensitive to antiherpetic agents such as acyclovir, valacyclovir and famciclovir and so administration of these antivirals may impair talimogene laherparepvec effectiveness.(1)

DISCUSSION: Agents that inhibit herpes simplex virus activity may impair the ability of talimogene laherparepvec to replicate and produce GM-CSF in tumors. The impact of concurrent antiviral and talimogene laherparepvec therapy has not been studied; patients requiring antiviral prophylaxis or treatment with acyclovir, valacyclovir and famciclovir were excluded from clinical trials.(1) Agents linked to this monograph are systemic formulations of acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, valacyclovir and valganciclovir.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Selected Antivirals/Vusolimogene Oderparepvec

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Vusolimogene oderparepvec is a genetically modified herpes simplex virus type 1 (HSV-1) oncolytic viral therapy.(1)

CLINICAL EFFECTS: Administration of antiviral agents with activity against HSV-1 may interfere with the effectiveness of vusolimogene oderparepvec.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving systemic antiviral treatment for herpetic infection should delay vusolimogene oderparepvec for 72 hours after completing antiviral therapy.(1)

DISCUSSION: Agents that inhibit herpes simplex virus activity may impair the ability of vusolimogene oderparepvec to replicate in tumors.(1) Antiviral agents with activity against HSV-1 include: acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, valacyclovir, and valganciclovir.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min

• Severe hepatic disease

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Less Frequent

• Neutropenic disorder

Rare or Very Rare

• Abnormal hepatic function tests
• Acute cognitive impairment
• Anaphylaxis
• Angioedema
• Erythema multiforme
• Hallucinations
• Hypersensitivity angiitis
• Leukopenia
• Obstructive hyperbilirubinemia
• Seizure disorder
• Skin rash
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Toxic epidermal necrolysis

More Frequent

• Diarrhea
• Headache disorder
• Nausea

Less Frequent

• Dizziness
• Dysmenorrhea
• Fatigue
• Flatulence
• Paresthesia
• Pruritus of skin
• Vomiting

Rare or Very Rare

• Drowsy
• Migraine
• Palpitations
• Urticaria

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Reproduction studies using oral famciclovir dosages up to 1 g/kg daily in rats and rabbits (approximately 3.6-21.6 and 1.8-10.8 times the human systemic exposure to penciclovir, respectively, based on AUC comparisons) and IV dosages of 360 mg/kg daily in rats (2-12 times the human dose based on body surface area comparisons) or 120 mg/kg daily in rabbits (1.5-9 times the human dose based on body surface area comparisons) have not revealed evidence of adverse effects on embryofetal development. Similar studies using IV penciclovir dosages up to 80 mg/kg daily in rats (0.4-2.6 times the human dose based on body surface area comparisons) or 60 mg/kg daily in rabbits (0.7-4.2 times the human dose based on body surface area comparisons) also did not reveal evidence of adverse effects on embryofetal development. There are no adequate and well-controlled studies to date using famciclovir in pregnant women, and the drug should be used during pregnancy only when clearly needed.

To monitor maternal-fetal outcome of pregnant women exposed to famciclovir, the manufacturer maintains a Famciclovir Pregnancy Registry. The registry may be contacted by calling 888-669-6682.

Reproduction studies using famciclovir or penciclovir in rats, mice, and dogs revealed evidence of testicular toxicity following repeated oral administration of high dosages. Testicular changes, including atrophy of the seminiferous tubules, reduction in sperm count, and/or increased incidence of sperm with abnormal morphology or reduced motility, were observed. The degree of toxicity was related to dose and duration of exposure. In male rats, decreased fertility was observed following 10 weeks of dosing at 500 mg/kg daily (1.9-11.4 times the human AUC). Administration of famciclovir to male rats in dosages of 50 mg/kg daily (0.2-1.2 times the human systemic exposure based on AUC comparisons) for 26 weeks did not reveal evidence of sperm or testicular toxicity. Testicular toxicity was observed following administration of dosages of 600 mg/kg daily (0.4-2.4 times the human systemic exposure based on AUC comparisons) for 104 weeks in male mice and dosages of 150 mg/kg daily (1.7-10.2 times the human system exposure based on AUC comparisons) for 26 weeks in male dogs. No effect on spermatogenesis was observed in human males with genital herpes following oral famciclovir dosages of 250 mg twice daily for 18 weeks.

It is not known whether famciclovir or penciclovir is distributed into milk in humans. Following oral administration of famciclovir to lactating rats, penciclovir was distributed into breast milk at concentrations higher than those observed in plasma. Data on safety of famciclovir in infants currently is not available.

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